The purpose of this grant is to define the nature of the autoimmune response in patients with idiopathic thrombocytopenic purpura (ITP) or immune mediated platelet production. We wish to determine the frequency and diversity of antiplatelet autoantibodies and to define the biochemistry and function of their target antigens. Over the past year, we have found that certain antiplatelet antibodies may be specific for aged or activated cells. As it is known that senescent platelets and erythrocytes accumulate immunoglobulin with aging and activation, we are currently examining the role of these autoantibodies in normal clearance of aged and activated cells. Activation antigens on platelets may be shared by other cells and may provide a probe to examine the role of these antigen membrane proteins in other cell lineages. The development of mouse anti-idiotypic antibodies is aiding in our ability to screen for the presence of these antibodies in plasma from normal individuals and patients with autoimmune disease. These studies have been expanded to determine the frequency of these idiotypes in other family members compared to non-related normal control plasmas, and examine whether certain idiotypes are more frequently associated with immune mediated thrombocytopenias. Biochemical characterization of the platelet antigens recognized by these human monoclonal autoantibodies continues to reveal a wide range of surface proteins and glycoproteins. At least five distinct patterns are seen on immunoblot; and two antibodies, A9 and 5E5, have been used to immunoprecipitate a Mr 230,000 and Mr 110,000 glycoprotein, respectively. The latter glycoprotein appears to be sensitive to thrombin treatment and we are currently examining whether this protein may represent the glycoprotein V, the thrombin receptor on platelets. Over the next year, we plan to extend our understanding of normal autoimmune response to antigens on aged or activated cells as will as the adherent expression of these activation antigens on transformed or malignant cells. (LB)